ANTIGEN-BINDING PROTEINS TARGETING S. AUREUS ORF0657n

Abstract

The present invention features antigen binding proteins that bind to a region found to have an epitope that can be targeted to provide protection against S. aureus infection. The region is designated herein as the “CS-D7” target region. The CS-D7 target region provides an S. aureus ORF0657n epitope that can be targeted to reduce the likelihood or severity of an S. aureus infection.

1 . An isolated antigen binding protein comprising a first variable region and a second variable region, wherein said first and second variable region binds to a CS-D7 target region. 
     
     
         2 . The binding protein of  claim 1 , wherein said first variable region is a heavy chain variable (V h ) region comprising at least one complementarity determining region (CDR) selected from the group consisting of:
 a first V h  CDR comprising SEQ ID NO: 46 or a sequence differing from SEQ ID NO: 46 by one amino acid;   a second V h  CDR comprising either SEQ ID NO: 36, SEQ ID NO: 38, SEQ ID NO: 39,   SEQ ID NO: 41, SEQ ID NO: 43 or SEQ ID NO: 44, or a sequence differing from SEQ ID NOs: 36, 38, 39, 41, 43, or 44 by one amino acid; and,   a third V h  CDR comprising either SEQ ID NO: 37, SEQ ID NO: 42 or SEQ ID NO: 45, or a sequence differing from SEQ ID NOs: 37, 42, or 45 by one amino acid.   
     
     
         3 . The binding protein of  claim 2 , wherein said V h  region comprises said first V h  CDR, said second V h  CDR and said third V h  CDR. 
     
     
         4 . The binding protein of  claim 3 , wherein said first, second and third V h  CDRs, respectively, comprise the amino acid sequences selected from the group consisting of:
 a) SEQ ID NO: 35, SEQ ID NO: 36 and SEQ ID NO: 37;   b) SEQ ID NO: 35, SEQ ID NO: 38 and SEQ ID NO: 37;   c) SEQ ID NO: 35, SEQ ID NO: 39 and SEQ ID NO: 37;   d) SEQ ID NO: 40, SEQ ID NO: 41 and SEQ ID NO: 42;   e) SEQ ID NO: 40, SEQ ID NO: 43 and SEQ ID NO: 45; and,   f) SEQ ID NO: 40, SEQ ID NO: 44 and SEQ ID NO: 42.   
     
     
         5 . The binding protein of  claim 2 , wherein said second variable region is a light chain variable (V l ) region comprising at least one complementarity determining region (CDR) selected from the group consisting of:
 a first V l  CDR comprising either SEQ ID NO: 17, SEQ ID NO: 20, SEQ ID NO: 23, SEQ ID NO: 26, SEQ ID NO: 29 or SEQ ID NO: 32, or a sequence differing from SEQ ID NOs: 17, 20, 23, 26, 29, or 32 by one amino acid;   a second V l  CDR comprising either SEQ ID NO: 18, SEQ ID NO: 21, SEQ ID NO: 24, SEQ ID NO: 27, SEQ ID NO: 30 or SEQ ID NO: 33, or a sequence differing from SEQ ID NOs: 18, 21, 24, 27, 30 or 33 by one amino acid; and,   a third V l  CDR comprising either SEQ ID NO: 19, SEQ ID NO: 22, SEQ ID NO: 25,   SEQ ID NO: 28, SEQ ID NO: 31 or SEQ ID NO: 34, or a sequence differing from SEQ ID NOs: 19, 22, 25, 28, 31, or 34 by one amino acid.   
     
     
         6 . The binding protein of  claim 5 , wherein said V l  region comprises said first V l  CDR, said second V l  CDR and said third V l  CDR. 
     
     
         7 . The binding protein of  claim 6 , wherein said first, second and third V l  CDRs, respectively, comprise the amino acid sequences selected from the group consisting of:
 a) SEQ ID NO: 17, SEQ ID NO: 18 and SEQ ID NO: 19;   b) SEQ ID NO: 20, SEQ ID NO: 21 and SEQ ID NO: 22;   c) SEQ ID NO: 23, SEQ ID NO: 24 and SEQ ID NO: 25;   d) SEQ ID NO: 26, SEQ ID NO: 27 and SEQ ID NO: 28;   e) SEQ ID NO: 29, SEQ ID NO: 30 and SEQ ID NO: 31; and,   f) SEQ ID NO: 32, SEQ ID NO: 33 and SEQ ID NO: 34.   
     
     
         8 . The binding protein of  claim 7 , wherein said binding protein is an antibody. 
     
     
         9 . The binding protein of  claim 8 , wherein said first V h  CDR, said second V h  CDR and said third V h  CDR, respectively, comprise SEQ ID NO: 35, SEQ ID NO: 36 and SEQ ID NO: 37; and, said first V l  CDR, said second V l  CDR, and said third V l  CDR, respectively, comprise SEQ ID NO: 17, SEQ ID NO: 18 and SEQ ID NO: 19. 
     
     
         10 . The binding protein of  claim 8 , wherein said V h  region comprises an amino acid sequence selected from the group consisting of amino acids 1-126 of SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 14 and SEQ ID NO: 16. 
     
     
         11 . The binding protein of  claim 10 , wherein said V l  region comprises an amino acid sequence selected from the group consisting of amino acids 1-108 of SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13 and SEQ ID NO: 15. 
     
     
         12 . The binding protein of  claim 8 , wherein said antibody comprises either:
 a) a V l  region comprising amino acids 1-108 of SEQ ID NO: 1 and a V h  region comprising amino acids 1-126 SEQ ID NO: 2;   b) a V l  region comprising SEQ ID NO: 3 and a V h  region comprising SEQ ID NO: 4;   c) a V l  region comprising SEQ ID NO: 5 and a V h  region comprising SEQ ID NO: 6;   d) a V l  region comprising SEQ ID NO: 7 and a V h  region comprising SEQ ID NO: 8;   e) a V l  region comprising SEQ ID NO: 9 and a V h  region comprising SEQ ID NO: 10;   f) a V l  region comprising SEQ ID NO: 11 and a V h  region comprising SEQ ID NO: 12;   g) a V l  region comprising SEQ ID NO: 13 and a V h  region comprising SEQ ID NO: 14;   Or,   h) V l  region comprising SEQ ID NO: 15 and a V h  region comprising SEQ ID NO: 16.   
     
     
         13 . The binding protein of  claim 12 , wherein said V h  region comprises amino acids 1-126 of SEQ ID NO: 2 and said V l  region comprises amino acids 1-108 of SEQ ID NO: 1. 
     
     
         14 . The binding protein of  claim 8 , wherein said antibody comprises a heavy chain comprising a hinge, CH 1 , CH 2 , and CH 3  regions from an IgG 1 , IgG 2 , IgG 3  or IgG 4  subtype; and a light chain comprising said V l  region, and either a human kappa C l  or human lambda C l . 
     
     
         15 . The binding protein of  claim 1 , wherein said binding protein is an antibody comprising a light chain which comprises SEQ ID NO: 1 and a heavy chain which comprises SEQ ID NO: 2. 
     
     
         16 . A nucleic acid comprising at least one recombinant gene that encodes an antigen binding protein heavy chain variable (V h ) region or an antigen binding protein light chain variable (V l ) region as described in  claim 5 . 
     
     
         17 . A nucleic acid of  claim 16 , wherein said nucleic acid comprises two recombinant genes, a first recombinant gene encoding the antigen binding protein V h  region and a second recombinant gene encoding the antigen binding protein V l  region. 
     
     
         18 . A recombinant cell comprising the recombinant nucleic acid of  claim 17 . 
     
     
         19 . A method of producing a protein comprising an antibody variable region comprising the steps of:
 a) growing the recombinant cell of  claim 18  under conditions wherein said protein is expressed; and,   b) purifying said protein.   
     
     
         20 . A pharmaceutical composition comprising the binding protein of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         21 . A method of protecting or treating against an  S. aureus  infection in a patient comprising the step of administering to said patient an effective amount of the binding protein of  claim 1 . 
     
     
         22 . The method of  claim 21 , wherein said patient is a human and said antigen binding protein is administered in conjunction with surgery or a foreign body implant. 
     
     
         23 . The method of  claim 21 , wherein said patient is a human infected with  S. aureus.    
     
     
         24 . (canceled) 
     
     
         25 . A polypeptide comprising an amino acid sequence with at least a 95% sequence identity to amino acids 42-342 of SEQ ID NO: 47, wherein said polypeptide is up to 350 amino acids in length.